Developmental Alterations of Intestinal SGLT1 and GLUT2 Induced by Early Weaning Coincides with Persistent Low-Grade Metabolic Inflammation in Female Pigs

2022 ◽  
Author(s):  
Yihang Li ◽  
Kyan M Thelen ◽  
Karina Matos Fernández ◽  
Rahul Nelli ◽  
Mahsa Fardisi ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Metabolic Diseases ◽  
Glucose Transporters ◽  
Later Life ◽  
Low Grade ◽  
Early Weaning ◽  
Early Life Adversity ◽  
Metabolic Inflammation ◽  
Transporter Protein ◽  
Increased Risk

Early life adversity (ELA) is linked with the increased risk for inflammatory and metabolic diseases in later life but the mechanisms remain poorly understood. Intestinal epithelial glucose transporters SGLT1 and GLUT2 are the major route for intestinal glucose uptake but have also received increased attention as modulators of inflammatory and metabolic diseases. Here we tested the hypothesis that early weaning (EW) in pigs, an established model of ELA, alters the development of epithelial glucose transporters and coincides with elevated markers of metabolic inflammation. Jejunum and ileum of 90 d old pigs previously exposed to EW (16 d wean age), exhibited reduced SGLT1 activity (by ~ 30%, P<0.05), compared with late weaned (LW, 26 d wean age) controls . In contrast, GLUT2-mediated glucose transport was increased (P = 0.003) in EW pigs compared with LW pigs. Reciprocal changes in SGLT1 and GLUT2-mediated transport coincided with transporter protein expression in the intestinal brush border membranes (BBM) that were observed at 90 d and 150 d of age. Ileal SGLT1-mediated glucose transport and BBM expression were Inhibited by the β-adrenergic receptor (βAR) blocker propranolol in EW and LW pigs. In contrast, propranolol enhanced ileal GLUT2-mediated glucose transport (P=0.015) and BBMV abundance (P=0.035) LW pigs, but not EW pigs. Early weaned pigs exhibited chronic elevated blood glucose and C-Reactive Protein (CRP) levels, and adipocyte hypertrophy and upregulated adipogenesis-related gene expression in visceral adipose tissue. Altered development of intestinal glucose transporters by EW could underlie the increased risk for later life inflammatory and metabolic diseases.

scholarly journals Early growth and postprandial appetite regulatory hormone responses

2013 ◽  
Vol 110 (9) ◽  
pp. 1591-1600 ◽  
Author(s):  
Mia-Maria Perälä ◽  
Eero Kajantie ◽  
Liisa M. Valsta ◽  
Jens J. Holst ◽  
Jaana Leiviskä ◽  
...  
Keyword(s):  
Test Meal ◽  
Metabolic Diseases ◽  
Hormone Secretion ◽  
Later Life ◽  
Early Growth ◽  
Birth Cohort Study ◽  
Slow Increase ◽  
Increased Risk ◽  
Hormone Responses ◽  
The Impact

Strong epidemiological evidence suggests that slow prenatal or postnatal growth is associated with an increased risk of CVD and other metabolic diseases. However, little is known whether early growth affects postprandial metabolism and, especially, the appetite regulatory hormone system. Therefore, we investigated the impact of early growth on postprandial appetite regulatory hormone responses to two high-protein and two high-fat content meals. Healthy, 65–75-year-old volunteers from the Helsinki Birth Cohort Study were recruited; twelve with a slow increase in BMI during the first year of life (SGI group) and twelve controls. Subjects ate a test meal (whey meal, casein meal, SFA meal and PUFA meal) once in a random order. Plasma glucose, insulin, TAG, NEFA, ghrelin, peptide tyrosine-tyrosine (PYY), glucose-dependent insulinotropic peptide, glucagon-like peptide-1 and a satiety profile were measured in the fasting state and for 4 h after each test meal. Compared with the controls, the SGI group had about 1·5-fold higher insulin responses after the whey meal (P= 0·037), casein meal (P= 0·023) and PUFA meal (P= 0·002). TAG responses were 34–69 % higher for the SGI group, but only the PUFA-meal responses differed significantly between the groups. The PYY response of the SGI group was 44 % higher after the whey meal (P= 0·046) and 115 % higher after the casein meal (P= 0·025) compared with the controls. No other statistically significant differences were seen between the groups. In conclusion, early growth may have a role in programming appetite regulatory hormone secretion in later life. Slow early growth is also associated with higher postprandial insulin and TAG responses but not with incretin levels.

scholarly journals The Impact of Ghrelin in Metabolic Diseases: An Immune Perspective

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Jéssica Aparecida da Silva Pereira ◽  
Felipe Corrêa da Silva ◽  
Pedro Manoel Mendes de Moraes-Vieira
Keyword(s):  
Immune Cells ◽  
Metabolic Diseases ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Low Grade ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Increased Risk ◽  
Inflammatory Profile ◽  
The Impact

Obesity and insulin resistance have reached epidemic proportions. Obesogenic conditions are associated with increased risk for the development of other comorbidities and obesity-related diseases. In metabolic disorders, there is chronic low-grade inflammation induced by the activation of immune cells, especially in metabolic relevant organs such as white adipose tissue (WAT). These immune cells are regulated by environmental and systemic cues. Ghrelin is a peptide secreted mainly by X/A-like gastric cells and acts through the growth hormone secretagogue receptor (GHS-R). This receptor is broadly expressed in the central nervous system (CNS) and in several cell types, including immune cells. Studies show that ghrelin induces an orexigenic state, and there is increasing evidence implicating an immunoregulatory role for ghrelin. Ghrelin mainly acts on the innate and adaptive immune systems to suppress inflammation and induce an anti-inflammatory profile. In this review, we discuss the immunoregulatory roles of ghrelin, the mechanisms by which ghrelin acts and potential pharmacological applications for ghrelin in the treatment of obesity-associated inflammatory diseases, such as type 2 diabetes (T2D).

Effect of physical training on glucose transporter protein and mRNA levels in rat adipocytes

1993 ◽  
Vol 265 (1) ◽  
pp. E128-E134 ◽  
Author(s):  
B. Stallknecht ◽  
P. H. Andersen ◽  
J. Vinten ◽  
L. L. Bendtsen ◽  
J. Sibbersen ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Physical Training ◽  
Glucose Transporter ◽  
Glucose Transporters ◽  
Intrinsic Activity ◽  
Mrna Levels ◽  
Glut 1 ◽  
Transporter Protein ◽  
Glut 4 ◽  
Adipocyte Volume

Physical training increases insulin-stimulated glucose transport and the number of glucose transporters in adipocytes measured by cytochalasin B binding. In the present study we used immunoblotting to measure the abundance of two glucose transporters (GLUT-4, GLUT-1) in white adipocytes from trained rats. Furthermore, the abundance of the mRNAs for these proteins and glucose transport was measured. Rats were swim-trained for 10 wk, and adipocytes were isolated from epididymal fat pads. The amount of GLUT-4/adipocyte volume unit was significantly higher in trained animals compared with both age- and cell size-matched animals. The amount of GLUT-4 mRNA was also increased by training and it decreased with increasing age. Furthermore, young age as well as training was accompanied by relatively low GLUT-4 protein/mRNA and relatively high overall GLUT-4 efficiency (recruitability and/or intrinsic activity). GLUT-1 protein and mRNA levels/adipocyte volume did not change with age or training.

The impact of maternal obesity on inflammatory processes and consequences for later offspring health outcomes

2017 ◽  
Vol 8 (5) ◽  
pp. 529-540 ◽  
Author(s):  
S. A. Segovia ◽  
M. H. Vickers ◽  
C. M. Reynolds
Keyword(s):  
Maternal Obesity ◽  
Intervention Strategy ◽  
Later Life ◽  
Developmental Programming ◽  
Health Concern ◽  
Low Grade ◽  
Metabolic Complications ◽  
Metabolic Inflammation ◽  
Inflammatory Processes ◽  
The Impact

Obesity is a global epidemic, affecting both developed and developing countries. The related metabolic consequences that arise from being overweight or obese are a paramount global health concern, and represent a significant burden on healthcare systems. Furthermore, being overweight or obese during pregnancy increases the risk of offspring developing obesity and other related metabolic complications in later life, which can therefore perpetuate a transgenerational cycle of obesity. Obesity is associated with a chronic state of low-grade metabolic inflammation. However, the role of maternal obesity-mediated alterations in inflammatory processes as a mechanism underpinning developmental programming in offspring is less understood. Further, the use of anti-inflammatory agents as an intervention strategy to ameliorate or reverse the impact of adverse developmental programming in the setting of maternal obesity has not been well studied. This review will discuss the impact of maternal obesity on key inflammatory pathways, impact on pregnancy and offspring outcomes, potential mechanisms and avenues for intervention.

scholarly journals The Effect of Dietary Protein Imbalance during Pregnancy on the Growth, Metabolism and Circulatory Metabolome of Neonatal and Weaned Juvenile Porcine Offspring

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3286
Author(s):  
Quentin L. Sciascia ◽  
Cornelia Prehn ◽  
Jerzy Adamski ◽  
Gürbüz Daş ◽  
Iris S. Lang ◽  
...  
Keyword(s):  
Porcine Model ◽  
Metabolic Diseases ◽  
Later Life ◽  
Metabolite Profile ◽  
Juvenile Period ◽  
Plasma Urea ◽  
Beta Alanine ◽  
Increased Risk ◽  
Offspring Growth ◽  
Urea Metabolism

Protein imbalance during pregnancy affects women in underdeveloped and developing countries and is associated with compromised offspring growth and an increased risk of metabolic diseases in later life. We studied in a porcine model the glucose and urea metabolism, and circulatory hormone and metabolite profile of offspring exposed during gestation, to maternal isoenergetic low–high (LP-HC), high–low (HP-LC) or adequate (AP) protein–carbohydrate ratio diets. At birth, LP-HC were lighter and the plasma acetylcarnitine to free carnitine ratios at 1 day of life was lower compared to AP offspring. Plasma urea concentrations were lower in 1 day old LP-HC offspring than HP-LC. In the juvenile period, increased insulin concentrations were observed in LP-HC and HP-LC offspring compared to AP, as was body weight from HP-LC compared to LP-HC. Plasma triglyceride concentrations were lower in 80 than 1 day old HP-LC offspring, and glucagon concentrations lower in 80 than 1 day old AP and HP-LC offspring. Plasma urea and the ratio of glucagon to insulin were lower in all 80 than 1 day old offspring. Aminoacyl-tRNA, arginine and phenylalanine, tyrosine and tryptophan metabolism, histidine and beta-alanine metabolism differed between 1 and 80 day old AP and HP-LC offspring. Maternal protein imbalance throughout pregnancy did not result in significant consequences in offspring metabolism compared to AP, indicating enormous plasticity by the placenta and developing offspring.

Childhood socioeconomic conditions are associated with increased chronic low-grade inflammation over adolescence: findings from the EPITeen cohort study

2020 ◽  
Vol 105 (7) ◽  
pp. 677-683 ◽  
Author(s):  
Sílvia Fraga ◽  
Milton Severo ◽  
Elisabete Ramos ◽  
Michelle Kelly-Irving ◽  
Susana Silva ◽  
...  
Keyword(s):  
Socioeconomic Position ◽  
Early Life ◽  
High Sensitivity ◽  
Low Grade ◽  
Socioeconomic Conditions ◽  
Early Life Adversity ◽  
Increased Risk ◽  
Health Related ◽  
Hs Crp ◽  
Low Grade Inflammation

ObjectiveEarly life adversity has been associated with increased risk of inflammation and inflammation-related diseases in adulthood. This study aimed to examine the association of childhood socioeconomic conditions with chronic low-grade inflammation over adolescence.MethodsWe used information on 2942 members (1507 girls and 1435 boys) of the EPITeen (Epidemiological Health Investigation of Teenagers in Porto) cohort that was established in 2003 in Porto, Portugal, and included 13-year-old adolescents were further evaluated at 17 and 21 years. Mother’ and father’s education and occupation were used as indicators of childhood socioeconomic conditions. High-sensitivity C reactive protein (hs-CRP) was measured at three points in time (13, 17 and 21 years). hs-CRP levels were categorised in tertiles separately for each wave; chronic low-grade inflammation in adolescence was defined as having hs-CRP levels in the highest tertile in at least two waves and never in the lowest tertile.ResultsPrevalence of chronic low-grade inflammation during adolescence was significantly higher among participants with low parental socioeconomic position. Low parental socioeconomic position was associated with chronic low-grade inflammation in adolescence, after adjustment for sex, perinatal and physical environment factors, health-related behaviours and health status in adolescence OR=1.6; 95% CI: 1.1 to 2.4 for lowest versus highest mother’s education and OR=1.6; 95% CI: 1.1 to 2.3 for lowest versus highest father’s occupation.ConclusionLow childhood socioeconomic conditions are associated with chronic low-grade inflammation during adolescence. Our results suggest that the early life socioeconomic environment has an impact on inflammatory processes over adolescence.

scholarly journals Adipocytokines in obesity and metabolic disease

2014 ◽  
Vol 220 (2) ◽  
pp. T47-T59 ◽  
Author(s):  
Haiming Cao
Keyword(s):  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Clinical Settings ◽  
Low Grade ◽  
Endocrine Organ ◽  
Metabolic Inflammation ◽  
The Past ◽  
Wide Range ◽  
Low Grade Inflammation

The current global obesity pandemic is the leading cause for the soaring rates of metabolic diseases, especially diabetes, cardiovascular disease, hypertension, and non-alcoholic hepatosteatosis. Efforts devoted to find cures for obesity and associated disorders in the past two decades have prompted intensive interest in adipocyte biology, and have led to major advances in the mechanistic understanding of adipose tissue as an essential endocrine organ. Adipose tissue secretes an array of hormones (adipokines) that signal key organs to maintain metabolic homeostasis, and their dysfunction has been causally linked to a wide range of metabolic diseases. In addition, obesity induces production of inflammatory cytokines (often referred to together with adipokines as adipocytokines) and infiltration of immune cells into adipose tissue, which creates a state of chronic low-grade inflammation. Metabolic inflammation has been increasingly recognized as a unifying mechanism linking obesity to a broad spectrum of pathological conditions. This review focuses on classic examples of adipocytokines that have helped to form the basis of the endocrine and inflammatory roles of adipose tissue, and it also details a few newly characterized adipocytokines that provide fresh insights into adipose biology. Studies of adipocytokines in clinical settings and their therapeutic potential are also discussed.

Possible effect of Astaxanthin on obesity related increased COVID-19 infection morbidity and mortality

2021 ◽  
Vol 17 ◽  
Author(s):  
Elif Didem Örs ◽  
Şenay Burçin Alkan ◽  
Abdullah Öksüz
Keyword(s):  
Metabolic Diseases ◽  
Positive Impact ◽  
Public Health Problem ◽  
World Health Organisation ◽  
Morbidity And Mortality ◽  
World Health ◽  
Low Grade ◽  
Global Public Health ◽  
Increased Risk ◽  
Anti Inflammatory

: Obesity is defined by the World Health Organisation (WHO) as a body mass index equals to 30 kg/m2 or greater. It is an important and escalating global public health problem. Obesity is known to cause low-grade chronic inflammation, increasing the burden of noncommunicable and possibly communicable diseases. There is considerable evidence that obesity is associated with an increased risk of contracting coronavirus disease 2019 (COVID-19) infection as well as significantly higher COVID-19 morbidity and mortality. It appears plausible that controlling the chronic systemic low-grade inflammation associated with obesity may have a positive impact on the symptoms and the prognosis of COVID-19 disease in obese patients. Astaxanthin (ASTX) is a naturally occurring carotenoid with anti-inflammatory, antioxidant, and immunomodulatory activities. As a nutraceutical agent, it is used as a preventative and a co-treatment in a number of systemic neurological, cardiovascular, and metabolic diseases. This review article will discuss the pathogenesis of COVID-19 infection and the effect of ASTX on obesity and obesity-related inflammation. The potential positive impact of ASTX anti-inflammatory properties in obese COVID-19 patients will be discussed.

scholarly journals Preeclampsia – long-term effects on mother and child

2021 ◽  
Vol 11 (8) ◽  
pp. 261-267
Author(s):  
Małgorzata Wieteska ◽  
Dominik Maj ◽  
Adrianna Gorecka ◽  
Bartłomiej Zaremba
Keyword(s):  
Metabolic Diseases ◽  
Later Life ◽  
Symptomatic Treatment ◽  
Diagnostic Methods ◽  
Hormonal Changes ◽  
Long Term Effects ◽  
Foetal Growth Restriction ◽  
Increased Risk ◽  
Mother And Child

Preeclampsia (PE) is a pregnancy complication that affects 5% to 8% of all pregnancies. It is a leading cause of maternal mortality that contributes annually more than 60,000 maternal deaths all over the world. Data submitted so far by clinicians are still insufficient to completely understand the disease. Despite many researches, the prediction of patients suffering from PE remains difficult. Moreover therapeutic methods are also limited and concentrated on symptomatic treatment and early termination of pregnancy. The  aim  of  the  presented  article  is  to  review  current research on the PE and its long-term effects on mother and child. PE is defined as a hypertension developing after 20 weeks of gestation with at least one of the following symptoms: proteinuria, maternal organ dysfunction or foetal growth restriction. Because initially patients may be completely asymptomatic, the diagnosis is usually difficult. Untreated PE may lead to the death of both mother and neonate. In later life it predisposes woman and child to cardiovascular and metabolic diseases. Maternal consequences are related to increased risk of hypertension, stroke, thrombosis or chronic kidney disease, whilst offspring implications are directly correlated with hypertension, increased body mass index, hormonal changes and reductions in cognitive functions. In the future there is a need to develop more effective diagnostic methods of PE. Comprehensive understanding of the pathophysiology would allow to avoid many negative long-term effects and reduce its mortality rate.

scholarly journals Does C-C Motif Chemokine Ligand 2 (CCL2) Link Obesity to a Pro-Inflammatory State?

2021 ◽  
Vol 22 (3) ◽  
pp. 1500
Author(s):  
Sebastian Dommel ◽  
Matthias Blüher
Keyword(s):  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Immune Cell ◽  
Current Knowledge ◽  
Low Grade ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tissue Macrophage ◽  
Metabolic Inflammation ◽  
Chemokine Ligand ◽  
Chemokine Ligand 2

The mechanisms of how obesity contributes to the development of cardio-metabolic diseases are not entirely understood. Obesity is frequently associated with adipose tissue dysfunction, characterized by, e.g., adipocyte hypertrophy, ectopic fat accumulation, immune cell infiltration, and the altered secretion of adipokines. Factors secreted from adipose tissue may induce and/or maintain a local and systemic low-grade activation of the innate immune system. Attraction of macrophages into adipose tissue and altered crosstalk between macrophages, adipocytes, and other cells of adipose tissue are symptoms of metabolic inflammation. Among several secreted factors attracting immune cells to adipose tissue, chemotactic C-C motif chemokine ligand 2 (CCL2) (also described as monocyte chemoattractant protein-1 (MCP-1)) has been shown to play a crucial role in adipose tissue macrophage infiltration. In this review, we aimed to summarize and discuss the current knowledge on CCL2 with a focus on its role in linking obesity to cardio-metabolic diseases.

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